Viral and clinical factors associated with the fulminant course of hepatitis A infection

Abstract

Fulminant hepatitis is a severe complication of hepatitis A virus infection. Its mechanism is unknown. Liver transplantation can be necessary, but spontaneous recovery is frequent. There are no data on the level of viral replication according to the clinical form of hepatitis A. We reviewed the files of 50 patients with acute hepatitis A. Nineteen patients had fulminant hepatitis (defined by encephalopathy and factor V <50%), and, from them, 10 patients underwent transplantation. Hepatitis A virus (HAV) RNA was quantified by real-time PCR on sera obtained at admission. The genotype was determined by phylogenetic analysis of HAV RNA. HAV RNA was detected in serum by RT-PCR in 39 out of 50 patients. Encephalopathy and low factor V level were significantly related to female gender, HAV PCR negativity (9/19 vs. 5/31, respectively; P ‫؍‬ .03), a low serum HAV RNA level (log, 3.6 ؎ 0.6 vs. 4.4 ؎ 0.9, respectively; P ‫؍‬ .02), genotypes other than IA, and acetaminophen intake. In multivariate analysis, low or undetectable HAV viral load and a high bilirubin level were independently associated with both low factor V levels and fulminant hepatitis and also with death or transplantation. In conclusion, HAV-related liver failure is due to an excessive host response associated with a marked reduction in viral load. The infection is spread chiefly by fecal-oral transmission and is a public health problem throughout the world. The main complication of HAV infection is fulminant hepatitis (FH), i.e., acute liver failure with encephalopathy, which occurs in less than 1% of cases. It appears to be more frequent in adults than in children. 1 In the United States, about one third of adults have anti-HAV antibodies, and 100 deaths per year are attributed to HAV-related acute liver failure. 1 This is also a frequent cause of death among children in developing countries. 2 Liver transplantation has markedly changed the prognosis of HAV-related acute liver failure in industrialized countries 3 and is currently indicated for patients with deep coma and low factor V levels. However, HAV-related FH resolves spontaneously more frequently than FH of other origins, and the decision to transplant or not to transplant is thus particularly difficult. Auxiliary liver transplantation may be appropriate in this setting, pending possible regeneration of the native liver. 4,5 Few data have been published on viral replication during acute hepatitis A, and viral load in patients with FH A has not yet been studied. There are several HAV genotypes, IA being most prevalent in industrialized countries. 6 Little information is available on the possible relation between the severity of hepatitis A and the infecting genotype. We applied real-time quantitative polymerase chain reaction (PCR) to stored sera from 50 patients with acute hepatitis A, of whom 19 had FH, to examine the possible relation between HAV viral load, HAV genotype, and the clinical course.

High and persistent excretion of hepatitis A virus in immunocompetent patients

“…No indication was found in this study that genotype influenced duration of jaundice or HAV excretion, nor did other studies looking for an association between HAV genotype and disease severity [Fujiwara et al, 2003;Rezende et al, 2003;Normann et al, 2004]. The findings show that HAV faecal excretion is high in the first month of illness, suggesting that patients may be infectious for a longer period than currently assumed.…”

“…These real-time PCRs target the 5 0 noncoding region and virus loads were quantified with an external standard [Costa-Mattioli et al, 2002b;Rezende et al, 2003;Normann et al, 2004].…”

“…One hypothesis is that hepatic disease is caused by the patient's immune system as it attempts to clear the virus [Vallbracht et al, 1986;Brack et al, 2002;Rezende et al, 2003]. Age and underlying disease, as well as medication, can influence disease outcome.…”

“…Age and underlying disease, as well as medication, can influence disease outcome. Rezende et al [2003] reported that patients with HAV-related fulminant hepatitis had low HAV levels in blood in spite of hepatocyte necrosis. This finding is in agreement with Sainokami et al [2005] who found that ALT levels and virus load were significantly correlated in patients with mild HAV-related symptoms, but not in those with severe symptoms.…”

Seroprevalence and Molecular Characterisation of Human Hepatitis A virus in Serum Samples of Tunisian Patients with Clinical Symptoms of Viral Hepatitis

“…The severity of hepatitis A is multifactorial, with age, gender, and drug toxicity [24]. HAV, member of the genus Hepatovirus of the Picornaviridae family, has been shown to be responsible for numerous disease outbreaks [5,8] related to personal and sexual contacts [3,6,9].…”